High risk of human immunodeficiency virus in men who have sex with men with HSV-2

HSV-2 infection is an important risk factor for HIV acquisition among men who have sex with men

What’s known?

• HSV-1 typically causes oropharyngeal infection, and transmission occurs primarily through personal contact during childhood, although it can also be transmitted sexually.
• HSV-2 is mainly associated with genital disease, and transmission is usually sexual.
• Both viruses can cause either anogenital or oropharyngeal infection.
• Genital HSV-2 infection increases the risk of human immunodeficiency virus (HIV) type 1 acquisition, likely via mucosal or epithelial disruption, which provides a portal of entry for HIV and via recruitment of CD4-positive T lymphocytes during HSV-2 reactivation.
   

What’s new?

• The relation between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) acquisition was evaluated among 4,295 high-risk, HIV-negative men who have sex with men in an intensive behavioural intervention (colloquially referred to as "EXPLORE") study in the United States from 1999 to 2003.
• Sexual behaviour data were obtained by computer-assisted self-interview, and sera were collected semi-annually for HIV and HSV-2 serology.
• HSV-2 infection was classified as ‘‘recent incident’’ (at the first HSV-2 seropositive visit), ‘‘remote incident’’ (within 24 months of the first positive visit), and ‘‘prevalent’’ (for visits >24 months after the first HSV-2 positive visit).
• Baseline HSV-2 prevalence was 20.3%.
• HSV-2 incidence was 1.9 per 100 person-years; significant risk factors were African-American race, unprotected receptive anal intercourse, an HIV-positive male sex partner, and six or more male partners in the prior 6 months.
• Overall HIV incidence was 1.9 (95% CI: 1.7, 2.2) per 100 person-years.
• HIV risk was elevated among men who have sex with men with recent incident HSV-2 (adjusted HR = 3.6, 95% CI: 1.7, 7.8), remote incident HSV-2 (adjusted HR = 1.7, 95% CI: 0.8, 3.3), and prevalent HSV-2 (adjusted HR = 1.5, 95% CI: 1.1, 2.1) infection compared with HSV-2 seronegative participants.
• The intensive, 10-session risk-reduction behavioural intervention tested in the EXPLORE study did not reduce HIV incidence to a statistically significant degree and had no effect on HSV-2 incidence, despite the statistically significant reduction in reported unprotected receptive anal intercourse.
• No herpes simplex virus type 1 (HSV-1) testing was done in this study and the finding that 17 percent of HSV-2 seronegative participants did report genital ulcer disease symptoms indicates that genital HSV-1 infections may have been relatively common in this cohort.
• It is evident from these data that HSV-2 infection is an important risk factor for HIV acquisition among men who have sex with men, although it remains uncertain whether incident HSV-2 confers additional risk compared with prevalent HSV-2.